The emergence of drug resistant pneumococcal disease is a significant public health problem. Risk factors include individual use of antibacterial drugs as well as social factors that promote human-to-human transmission of the pathogen. In addition, the introduction of a new vaccine for use in children has resulted in strong selective forces that are changing the epidemiology of this disease. Understanding the relationship between these forces is a critical component of efforts to design programs to preserve the efficacy of antimicrobial drugs for the future. Few studies have considered the geographic nature of this problem in analyzing the relationship between individual and community-level risk factors. The proposed study is a novel merger of geographical, epidemiological and microbiological analytic strategies to identify factors that promote the spread of drug resistant pneumococci. Our primary aim is to compare the serological, molecular, and geographic distributions of macrolide resistant and macrolide susceptible pneumococci over the Southeastern Pennsylvania region. Our hypothesis is that antibiotic susceptibility displays significant geographic heterogeneity over a small region and that heterogeneity reveals small-area characteristics, which increase the spread of drug resistant S. pneumoniae. The proposed study is a population-based case-control study to compare the individual and community level characteristics of patients with drug resistant and susceptible pneumococcal bacteremia with a focus on macrolide resistant infections. By identifying all bacteremic pneumococcal infections within a 5 county region, we will be able to examine small area heterogeneity in the levels of drug susceptibility. Serological and molecular typing of all isolates will permit separate analyses for geographic heterogeneity within subgroups of isolates that are clonally related as well as assess the impact of vaccine strategies on the spread of drug resistance. Statistical analyses incorporating multilevel and diffusion models will examine spatial and temporal relationships over a six-year period in order to determine the relative impact of individual and community-level factors on the spread of drug resistant pneumococcal infections. This proposal is a competitive renewal of an ongoing population-based case-control study to develop a prediction rule for penicillin drug resistance among patients with bacteremic pneumococcal pneumonia. The proposed study will maintain our enrollment over an additional three years in order to complete six-years of active enrollment and achieve the necessary sample size for the proposed molecular and geographic analyses.